Factor VII is a plasma coagulation factor, which, once activated to Factor VIIa, initiates the normal haemostatic process by forming a complex with tissue factor (TF), a cell surface glycoprotein that is exposed to the circulation as a result of injury to the vessel wall. Subsequently, the Factor VIIa-TF complex activates Factor IX and Factor X into their activated forms (Factor IXa and Factor Xa, respectively). Factor Xa converts limited amounts of prothrombin to thrombin on the tissue factor-bearing cell. Thrombin activates platelets and Factors V and VIII into Factors Va and VIIIa, both cofactors in the further process leading to the full thrombin burst. Thrombin finally converts fibrinogen to fibrin resulting in formation of a fibrin clot. Fibrin clots formed in the presence of high thrombin concentrations comprise a tighter network and are more resistant to proteolysis than clots formed in lower concentrations of thrombin. Accordingly, a full thrombin burst is likely to be important for forming a hemostatic plug that is resistant to fibrinolysis and thus to facilitate full hemostasis and wound healing.
Factor VIIa, as well as Factor VIII and Factor IX, have been used to control bleeding disorders that are caused by clotting factor deficiencies (such as, e.g. haemophilia A and B or deficiency of coagulation Factors XI or VII) or clotting factor inhibitors. Factor VIIa has also been used to control excessive bleeding caused by defective platelet function, thrombocytopenia or von Willebrand's disease.
Typically, however, patients are treated with multiple injections or infusions of a coagulation factor before the bleeding is stopped. In the case of Factor VIII and Factor IX administration, a considerable number of injections are needed to maintain haemostasis until the injury causing the bleeding is completely healed. A quicker and more effective treatment, as well as a reduction in the number of injections needed before the bleeding is stopped, represent important benefit to such patients. It would also be a considerable benefit to a patient needing frequent injections or infusions with a haemostatic agent that the injection frequency be reduced.
Thus, there is a need in the art for methods for preventing and/or treating bleeding episodes that reduce the duration of administration and provide a more rapid hemostasis.